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Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Precision Medicine is being increasingly used in the developed world to improve health care. While several Precision Medicine (PM) initiatives have been launched worldwide, their implementations have proven to be more challenging particularly in low- and middle-income countries. To address this issue, the “Personalized Medicine in North Africa” initiative (PerMediNA) was launched in three North African countries namely Tunisia, Algeria and Morocco. PerMediNA is coordinated by Institut Pasteur de Tunis together with the French Ministry for Europe and Foreign Affairs, with the support of Institut Pasteur in France. The project is carried out along with Institut Pasteur d’Algérie and Institut Pasteur du Maroc in collaboration with national and international leading institutions in the field of PM including Institut Gustave Roussy in Paris. PerMediNA aims to assess the readiness level of PM implementation in North Africa, to strengthen PM infrastructure, to provide workforce training, to generate genomic data on North African populations, to implement cost effective, affordable and sustainable genetic testing for cancer patients and to inform policy makers on how to translate research knowledge into health products and services. Gender equity and involvement of young scientists in this implementation process are other key goals of the PerMediNA project.In this paper, we are describing PerMediNA as the first PM implementation initiative in North Africa. Such initiatives contribute significantly in shortening existing health disparities and inequities between developed and developing countries and accelerate access to innovative treatments for global health.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Abstract The work described below explores the field of the effects of pulsed radiofrequency for pain relief purposes. While the effects of this technique on pain modulation (A-delta and C fibers) are relatively well-known, little has been written yet about the potential of pulsed radiofrequency interactions with other fibers. The proposed algorithm, specifically elaborated, investigates the effect of this technique on neuromuscular fatigue, through a surface electromyographic study of the femoral nerve of a patient with residual pain after knee arthroplasty surgery, before and after the treatment. This work yields a preliminary result that is encouraging for subsequent large-scale studies.

Abstract Background Breast cancer in Tunisia is often diagnosed at a late stage with long delay in time to consultation and to diagnosis.The aim of this study is to estimate the sensitivity and specificity of the transcutaneous breast cancer detection by canine olfactionin Tunisian women and to identify the potential confounding factors. Methods This is a diagnostic case control study that took place from October 2021 to November 2022 in the Department of Medical Oncology at the University Hospital Farhat Hached of Sousse and in the security and training dog center located in Sousse (K9 Dog Center Security & Training). A two-year-old male Belgian Malinois was trained to detect breast cancer on skin secretion samples in compresses that had been worn overnight by women on their breast and then a double-blind testing was performed. There was no contact between women and the dog. From the mentioned responses of the dog, four parameters were calculated: sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV). Results Two hundred women were included in this trial: 100 breast cancer (BC) patients recruited from Farhat Hached University Hospital of Sousse and 100 healthy volunteers (HV).The calculated sensitivity was 84% (95% CI 78–89%) and the calculated specificity was 81% (95% CI 75–86%). The calculated predictive values were: PPV = 83,51% (95% CI 78,37–88,65%) and NPV = 81,55% (95% CI 76.17–86.93%). In the multivariate study, only four confounding factors of test’s sensitivity were retained: age (OR = 1.210 [95% CI = 1.085–1.349]; p = 0.001), history of diabetes(OR = 0.017 [95% CI = 0.001–0.228]; p = 0.002), sampling at hospital (OR = 0.010 [95% CI = 0.003–0.464]; p = 0.010) and testing during chemotherapy courses (OR = 0.034 [95% CI = 0.003–0.404]; p = 0.007).For test’s specificity, we retained the three following confounding factors: age (OR = 1,104 [95% CI = 1.021–1.195]; p = 0.014), history of benign mastopathy (OR = 0.243 [95% CI = 0.074–0.805]; p = 0.021)and history of arterial hypertension (OR = 0.194 [95% CI = 0.053–0.707]; p = 0.013). Conclusion This is a pilot study that opens new avenues in developing a reliable cancer diagnostic tool that integrates the dog's olfactory ability to detect breast cancer using a transcutaneous sampling method. It could be a pre-test to select patients who are eligible to a screening mammogram, especially in low-income countries where there is no national mammography screening program. Pactr.org identifier PACTR202201864472288, registration date 11/01/2022.

Marine fungi communities play a crucial role in the recycling of nutrients, restoration of biological systems, and the overall functioning of ecosystems. While aquatic fungal communities do react to pollution, there is a significant lack of information regarding the changes in the fungal community's structure, caused by marine pollution. In this study, we aim to address this gap in knowledge by investigating the range and makeup of fungal species present in marine environments in a polluted bay in Tunisia, spanning a biodiversity hotspot (Monastir Bay). Sequence analysis of the internal transcribed spacer region from culturable mycobiome and physicochemical parameters were investigated at seven sites in the bay. A total of 32 fungal taxa were identified at the genus and/or species levels and were assigned to four major groups (Aspergillacae 37.5%, Dothiomyceta 21.87%, Sordariamyceta 28.12%, and Yeasts 12.5%) with a remarkable predominance of Aspergillus genus. Assessment of the Shannon–Wiener diversity index and the Simpson dominance index revealed that the highest species diversity index (0.84) was recorded at the Kheniss site. Our results suggest the existence of diverse fungal communities, can be considered a useful community model for further ecological and evolutionary study of fungi in the bay. HIGHLIGHTS The biodiversity of marine fungi and their ecological roles in the coastal environment of Tunisia are deeply unknown.; A total of 32 fungal taxa were assigned to four major groups (Aspergillacae 37.5%, Dothiomyceta 21.87%, Sordariamyceta 28.12%, and Yeasts 12.5%).; Remarkable predominance of Aspergillus genus is observed.; The highest fungal taxonomic biodiversity was found in organically rich waters.;

Snakebite envenoming (SBE) remains a severely neglected public health issue, particularly affecting tropical and subtropical regions, with Africa experiencing an estimated 435,000 to 580,000 snakebites annually, leading to high morbidity and mortality rates, especially across Africa and Asia. Recognized as a Neglected Tropical Disease, SBE management is further complicated by the inadequate efficacy of current antivenom treatments. Of particular concern are cobras (Naja sp.), whose neurotoxins can induce rapid fatal respiratory paralysis. In this study, we investigate the potential of nanobodies as a promising next-generation of immunotherapeutics against cobra venoms. Through a dual strategy of the characterization of venom toxic fractions from cobras captured for the first time in Algeria and Tunisia biotopes, coupled with in vitro assays to evaluate their interactions with acetylcholine receptors, and subsequent immunization of dromedaries to produce specific nanobodies, we identified two lethal fractions, F5 and F6, from each venom, and selected five nanobodies with significant binding and neutralizing of 3DL50 (0.74 mg/kg). The combination of these nanobodies demonstrated a synergistic effect, reaching 100% neutralizing efficacy of 2DL50 lethal venom fraction (0.88 mg/kg) doses in mice. Additionally, our findings highlighted the complex mechanism of cobra venom action through the lethal synergism among its major toxins.

This study focused on the evaluation of the phytotoxic activity of four essential oils (EOs) from the Mediterranean species of Thymus sp. pl., namely Thymus algeriensis Boiss. et Reut., T. ciliatus Desf. subspecies coloratus (Boiss. et Reut.) Batt., T. vulgaris L. ecotype Fasano and T. vulgaris cultivar L. Varico 3, to identify new biomolecules with herbicide potential. The chemical characterization of EOs was performed by GC-MS. The evaluation of the phytotoxicity of the EOs was conducted under in vitro conditions, and the inhibition of germination and seedling growth of Lolium perenne L. and Amaranthus retroflexus L. were assessed. Five concentrations (100, 250, 500, 750 and 1000 µL/100 mL) were considered. Phytochemical analysis revealed a great diversity of compounds. T. algeriensis and T. ciliatus EOs were characterized by the absence of carvacrol and a low content of thymol in T. ciliatus. On the contrary, T. vulgaris ecotype Fasano and T. vulgaris cultivar Varico 3 were characterized by an important content of p-cymene, thymol and carvacrol. All the EOs expressed a potent phytotoxic activity against the tested species. The total inhibition of seed germination and seedling growth were recorded for the highest concentrations of all the EOs. T. vulgaris ecotype Fasano expressed the most effective activity.

Chalcones constitute an important group of natural compounds abundant in fruits and comestible plants. They are a subject of increasing interest because of their biological activities, including anti-diabetic and anti-obesity effects. The simple chalcone structural scaffold can be modified at multiple sites with different chemical moieties. Here, we generated an artificial chalcone, i.e., 3,5-dimethyl-2,4,6-trimethoxychalcone (TriMetChalc), derived from 2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC). DMC is a major compound of Cleistocalyx operculatus, a plant widely used in Asia for its anti-hyperglycemic activity. Using ob/ob mice as an obesity model, we report that, after 3 weeks of per os administration, TriMetChalc modified food intake through the specific activation of brain structures dedicated to the regulation of energy balance. TriMetChalc also decreased weight gain, glucose intolerance, and hepatic steatosis. Moreover, through extensive liver lipidomic analysis, we identified TriMetChalc-induced modifications that could contribute to improving the liver status of the animals. Hence, TriMetChalc is a chalcone derivative capable of reducing food intake and the addition of glucose intolerance and hepatic steatosis in a mouse model of obesity. In light of these results, we believe that TriMetChalc action deserves to be more deeply evaluated over longer treatment periods and/or in combination with other chalcones with protective effects on the liver.

Objective: This study compared postural control and neuromuscular activation in athletic swimmers (A-S) and non-athletic swimmers (N-A-S) in older children. Methods: Ten A-S and ten N-A-S underwent assessments of center of pressure (CoP) parameters under static and dynamic surfaces in two directions (dynamic mediolateral (DML) and dynamic anteroposterior (DAP)) in eyes-open (EO) and eyes-closed (EC) conditions, and electromyography (EMG) parameters under DAP and DML directions in EO and EC conditions. Results: Results showed that A-S demonstrated significantly superior postural control (p < 0.05), with smaller CoP area and lower CoP mean velocity compared with N-A-S, particularly in static with EC, DAP with EO and EC, and DML with EO conditions. A-S exhibited significantly larger neuromuscular activation amplitudes (p < 0.05), especially in the AP direction. Conclusions: These findings suggested that athletic swimming training may enhance postural control and neuromuscular activation in 11–13-year-old children, emphasizing the potential benefits of incorporating swimming exercises in these children.

Adhesive capsulitis is a pathology that affects the shoulder and can have a particularly long and disabling course. The usual therapies are treatment with non-steroidal anti-inflammatory drugs (NSAID) and painkillers, steroid injections, physiotherapy, and surgical treatment. This case report describes the effect of a single treatment with pulsed radiofrequency of the suprascapular nerve in a diabetic patient affected by this pathology, for whom steroid injections were contraindicated. Three weeks after the treatment, the reduction of pain and the improvement of ROM (range of movement) allowed the patient to start an adequate physiotherapy treatment, which was not feasible until that moment due to the severe pain despite NSAIDS therapy. The peculiarity of this work consists in the accurate measure of the impact of the analgesic treatment alone in improving the ROM and muscular activation in the patient. The patient was able to correctly perform physiotherapy only once the pain was reduced, after PRF (pulsed radio frequency) treatment. This study has two limitations: being a case report and not a prospective randomized study, and observing the kinematic and pain aspects for a limited period of time. Finally, the case report draws attention to the importance of cooperation between the various health figures involved in the treatment of patients suffering from adhesive capsules.

Microbial pollution in marine environments is one of the critical issues with regard to the sanitary status of recreational activities and seafood harvesting due to a potential contamination by pathogenic microorganisms. This review's objectives were to identify instances of bacterial, viral and protozoan parasite pollution in the Tunisian coastal region and to make recommendations for further research. Fecal indicators such as Escherichia coli and Salmonella spp. were detected in samples of clams and mussels. Vibrionaceae species were also recorded in seawater, sediment, fish and clams in different sites from north to south with the dominance of Vibrio alginolyticus. Bivalve mollusks collected from the Tunisian coast have been revealed to harbor viruses as well as protozoan parasites. Furthermore, the isolation of multidrug-resistant bacterial strains from Tunisian coastlines proves the significant spread and circulation of antibiotic resistance caused by the massive use of antibiotics. In conclusion, we suggest intensive monitoring and cutting-edge wastewater treatment technologies to enhance seawater quality and preserve the biodiversity of aquatic life. Rapid detection techniques for the most important pathogenic microorganisms in seafood and seawater must be also developed to reduce human health risk. HIGHLIGHTS Monitoring the microbial quality of the Tunisian coast environment is crucial.; Wastewater discharge was the main cause of microbial pollution and the spread of multi-resistant strains.; Improvement of wastewater treatment procedure is highly recommended to reduce the pollutant loads to the sea.; More investigations should be conducted especially for viral and parasitic contamination.;

The first few days of life are characterized by rapid external and internal changes that require substantial immune system adaptations. Despite growing evidence of the impact of this period on lifelong immune health, this period remains largely uncharted. To identify factors that may impact the trajectory of immune development, we conducted stringently standardized, high-throughput phenotyping of peripheral white blood cell (WBC) populations from 796 newborns across two distinct cohorts (The Gambia, West Africa; Papua New Guinea, Melanesia) in the framework of a Human Immunology Project Consortium (HIPC) study. Samples were collected twice from each newborn during the first week of life, first at Day of Life 0 (at birth) and then subsequently at Day of Life 1, 3, or 7 depending on the randomization group the newborn belongs to. The subsequent analysis was conducted at an unprecedented level of detail using flow cytometry and an unbiased automated gating algorithm. The results showed that WBC composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes across days of life were most pronounced in the innate myeloid compartment. Breastfeeding, and at a smaller scale neonatal vaccination, were associated with changes in peripheral blood neutrophil and monocyte cell counts. Our results suggest a common trajectory of immune development in newborns and possible association with timing of breastfeeding initiation, which may contribute to immune-mediated protection from infection in early life. These data begin to outline a specific window of opportunity for interventions that could deliberately direct WBC composition, and with that, immune trajectory and thus ontogeny in early life. This trial is registered with NCT03246230.

IntroductionBreast cancer disease often affects the ipsilateral shoulder joint, with pain and joint limitation. Proper pain management, which can be obtained using, for example, pulsed radiofrequency of the suprascapular nerve, can help the physiotherapist mitigate patient pain. The modern technologies of kinematic analysis and surface electromyography of movement analysis can give further support in building a personalized rehabilitation program, based on the quantitative study of movement, in this case of the upper limb.MethodsA brief case report was conceived to develop and test the evolution of a shoulder joint analysis protocol based on an inertial accelerometer and non-invasive surface electromyography.ResultsAn analysis algorithm was defined to adapt to the needs of patients operated on at the breast based on a kinematic component (ROM - range of movement - and Jerk index) and an electromyographic one (study of muscle behavior in groups of four). The coactivations were also evaluated, both as an average value and in graphical form, to offer the physiotherapist a complete overview of the movement of the upper limb.DiscussionThe promising protocol results underline its strengths, including the simplicity of use, combined with the reduced time required for processing the reports and the portability of the PC-sensors complex, making these analyses potentially valuable for patient care.

Maternal immunisation, a low cost and high efficacy intervention is recommended for its pathogen specific protection. Evidence suggests that maternal immunisation has another significant impact: reduction of preterm birth (PTB), the single greatest cause of childhood morbidity and mortality globally. Our overarching question is: how does maternal immunisation modify the immune system in pregnant women and/or their newborn to reduce adverse pregnancy outcomes and enhance the newborn infant’s capacity to protect itself from infectious diseases during early childhood? To answer this question we are conducting a multi-site, prospective observational cohort study collecting maternal and infant biological samples at defined time points during pregnancy and post-partum from nulliparous women. We aim to enrol 400 women and determine the immune trajectory in pregnancy and the impact of maternal immunisation (including influenza, pertussis and/or COVID-19 vaccines) on this trajectory. The results are expected to identify areas that can be targeted for future intervention studies.

Tunisia has a long tradition of viticulture, and the grapevine is used for a variety of traditional foods. The country has many plant-based dishes, which may have different compositions and names depending on the region of origin. Unfortunately, over the years, traditional preparations are no longer as popular as they used to be, due to both changing lifestyles and the introduction of new crops and foods. For example, the use of grapevine in traditional dishes has declined as traditions have been lost and habits have changed in favor of new, ready-to-eat foods. The close link between grapevine, culture and territory requires an appropriate evaluation and characterization of traditional foods in order to enhance and extend their use, ensure their sustainability and preserve the varieties used to produce them. This review analyzes the use of local grapevine varieties in different traditional dishes as a means to preserve an invaluable natural and cultural resource and heritage.

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

ABSTRACT Many eukaryotic membrane-dependent functions are often spatially and temporally regulated by membrane microdomains (FMMs), also known as lipid rafts. These domains are enriched in polyisoprenoid lipids and scaffolding proteins belonging to the stomatin, prohibitin, flotillin, and HflK/C (SPFH) protein superfamily that was also identified in Gram-positive bacteria. In contrast, little is still known about FMMs in Gram-negative bacteria. In Escherichia coli K-12, 4 SPFH proteins, YqiK, QmcA, HflK, and HflC, were shown to localize in discrete polar or lateral inner membrane locations, raising the possibility that E. coli SPFH proteins could contribute to the assembly of inner membrane FMMs and the regulation of cellular processes. Here, we studied the determinant of the localization of QmcA and HflC and showed that FMM-associated cardiolipin lipid biosynthesis is required for their native localization pattern. Using Biolog phenotypic arrays, we showed that a mutant lacking all SPFH genes displayed increased sensitivity to aminoglycosides and oxidative stress that is due to the absence of HflKC. Our study therefore provides further insights into the contribution of SPFH proteins to stress tolerance in E. coli. IMPORTANCE Eukaryotic cells often segregate physiological processes in cholesterol-rich functional membrane microdomains. These domains are also called lipid rafts and contain proteins of the stomatin, prohibitin, flotillin, and HflK/C (SPFH) superfamily, which are also present in prokaryotes but have been mostly studied in Gram-positive bacteria. Here, we showed that the cell localization of the SPFH proteins QmcA and HflKC in the Gram-negative bacterium E. coli is altered in the absence of cardiolipin lipid synthesis. This suggests that cardiolipins contribute to E. coli membrane microdomain assembly. Using a broad phenotypic analysis, we also showed that HflKC contribute to E. coli tolerance to aminoglycosides and oxidative stress. Our study, therefore, provides new insights into the cellular processes associated with SPFH proteins in E. coli.

Summary: Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNβ-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 μg subcutaneous pegylated IFNβ-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNβ-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNβ-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = −0.2%, 95% CI = −8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = −3.6% to 11.3%). Treatment with IFNβ-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNβ-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as ‘Plegridy (peginterferon beta-1a).’ The study was substantially funded by BHP Holdings Pty Ltd.

Background Nutrition is the most important environmental factor in the development and progression of childhood obesity, which is very common in Arabic countries.Aim Study of associated factors and nutritional status of childhood obesity.Methods This was a comparative study of 50 obese children recruited from the outpatient department of the children’s hospital, as well as 35 controls. The two groups were matched for gender and age. Anthropometric measurements have been undertaken. A food history as well as a frequency of consumption of certain foods were performed.Results There were 32 girls in obese group. Breastfeeding was more common in the control group (p = 0.04) but gestational diabetes, pregnancy weight gain, and macrosomia were greater in obese people (p = 0.002; 0.0001 and 0.004) . Food diversification was early in the obese (p = 0.05). Mobile phone use was higher among obese people (p = 0.001) but time spent watching TV was not significant (p = 0.06). There was no significant difference between the two groups regarding: the number of hours of sleep, and the practice of sport. Sedentary lifestyle concerned 34% of obese versus 8.57% controls. Intense physical activity was practiced by 14.29% of the controls against any obese (p = 0.0001). The anthropometric parameters of the parents of the obese were more important than those of the controls. The average BMI of the obese was 25.63 Kg/m2.The frequency of consumption showed a more caloric and fat diet in obese group.The diet of the controls was richer in proteins and lipids but better distributed in MUFA and PUFA, but the energy intake of the obese was significantly higher (10,612 versus 4097 Kcal/d). The mineral and vitamin intakes of the obese were correct.Conclusions The fight against childhood obesity essentially involves prevention and promotion of a good lifestyle.

Abstract Microglia are involved in neuroinflammatory processes during diverse pathophysiological conditions. To date, the possible contribution of these cells to deoxynivalenol (DON)-induced brain inflammation and anorexia has not yet been evaluated. DON, one of the most abundant trichothecenes found in cereals, has been implicated in mycotoxicosis in both humans and farm animals. DON-induced toxicity is characterized by reduced food intake, weight gain, and immunological effects. We previously showed that exposure to DON induces an inflammatory response within the hypothalamus and dorsal vagal complex (DVC) which contributes to DON-induced anorexia. Here, in response to anorectic DON doses, we reported microglial activation within two circumventricular organs (CVOs), the area postrema (AP) and median eminence (ME) located in the DVC and the hypothalamus, respectively. Interestingly, this microglial activation was observed while DON-induced anorexia was ongoing (i.e., 3 and 6 h after DON administration). Next, we took advantage of pharmacological microglia deletion using PLX3397, a colony-stimulating factor 1 receptor (CSF1R)-inhibitor. Surprisingly, microglia-depleted mice exhibited an increased sensitivity to DON since non-anorectic DON doses reduced food intake in PLX3397-treated mice. Moreover, low DON doses induced c-Fos expression within feeding behavior-associated structures in PLX3397-treated mice but not in control mice. In parallel, we have highlighted heterogeneity in the phenotype of microglial cells present in and around the AP and ME of control animals. In these areas, microglial subpopulations expressed IBA1, TMEM119, CD11b and CD68 to varying degrees. In addition, a CD68 positive subpopulation showed, under resting conditions, a noticeable phagocytotic/endocytotic activity. We observed that DON strongly reduced CD68 in the hypothalamus and DVC. Finally, inactivation of constitutively active microglia by intraperitoneal administration of minocycline resulted in anorexia with a DON dose ineffective in control mice. Taken together, these results strongly suggest that various populations of microglial cells residing in and around the CVOs are maintained in a functionally active state even under physiological conditions. We propose that these microglial cell populations are attempting to protect the brain parenchyma from hazardous molecules coming from the blood. This study could contribute to a better understanding of how microglia respond to environmental contaminants.

Objectives No consensus criteria describe the medical eligibility of the patients to intermediate care units (IMCUs). In this first part of the UNISURC project, we aimed to develop criteria based on a consensus of physicians from the main specialties involved in IMCU admission decisions.Design We selected criteria from IMCU literature, scoring systems and intensive care unit nursing workload. We submitted these criteria to a panel of experts in a Delphi survey. We used a two-round Delphi survey procedure to assess the validity and feasibility of each criterion.Setting Medical practitioners in either public or private French institutions and proposed by the national scientific societies of anaesthesiology, emergency medicine and intensive care. The Delphi rounds took place in 2015–2016.Outcome measures Validity and feasibility of the proposed criteria; uniformity of the judgement across the primary specialty and the hospital category of the responders.Results The criteria submitted to vote were classified as one of: chronic factor (CF); acute factor (AF); specific pathway (SP); nursing activity (NA) and hospital environment (HE). Of 189 experts invited, 81 (41%) responded to the first round and 62 of them (76%) responded to the second round. A definite selection of 63 items was made, distributed across 6 CF, 18 AF, 31 SP, 3 NA and 5 HE. Validity and feasibility were influenced by the specialty or the public/private status of the institution of the responders for a few items.Conclusion We created a set of 63 consensus criteria with acceptable validity and feasibility to assess the medical eligibility of the patients to IMCUs. The second part of the UNISURC project will assess the distribution of each criterion in a prospective multicentre national cohort.Trial registration number NCT02590172.

Background and aim: A better understanding of resistance to checkpoint inhibitors is essential to define subsequent treatments in advanced non-small cell lung cancer. By characterizing clinical and radiological features of progression after anti-programmed death-1/programmed death ligand-1 (anti-PD-1/PD-L1), we aimed to define therapeutic strategies in patients with initial durable clinical benefit. Patients and methods: This monocentric, retrospective study included patients who presented progressive disease (PD) according to RECIST 1.1 criteria after anti-PD-1/PD-L1 monotherapy. Patients were classified into two groups, “primary resistance” and “Progressive Disease (PD) after Durable Clinical Benefit (DCB)”, according to the Society of Immunotherapy of Cancer classification. We compared the post-progression survival (PPS) of both groups and analyzed the patterns of progression. An exploratory analysis was performed using the tumor growth rate (TGR) to assess the global growth kinetics of cancer and the persistent benefit of immunotherapy beyond PD after DCB. Results: A total of 148 patients were included; 105 of them presented “primary resistance” and 43 “PD after DCB”. The median PPS was 5.2 months (95% CI: 2.6–6.5) for primary resistance (p < 0.0001) vs. 21.3 months (95% CI: 18.5–36.3) for “PD after DCB”, and the multivariable hazard ratio was 0.14 (95% CI: 0.07–0.30). The oligoprogression pattern was frequent in the “PD after DCB” group (76.7%) and occurred mostly in pre-existing lesions (72.1%). TGR deceleration suggested a persistent benefit of PD-1/PD-L1 blockade in 44.2% of cases. Conclusions: PD after DCB is an independent factor of longer post-progression survival with specific patterns that prompt to contemplate loco-regional treatments. TGR is a promising tool to assess the residual benefit of immunotherapy and justify the continuation of immunotherapy in addition to radiotherapy or surgery.

After a lull of >20 years, Algeria experienced a cholera outbreak in 2018 that included 291 suspected cases. We found that outbreak isolates were Vibrio cholerae O1 serotype Ogawa from seventh pandemic El Tor sublineage AFR14, which corresponds to a new introduction of cholera into Africa from South Asia.

Abstract Introduction The management of obesity is difficult with many failures of lifestyle measures, hence the need to broaden the range of treatments prescribed. The aim of our work was to study the influence of pre and probiotics on weight loss psychological profile and metabolic parameters in obese patients. Methods It is a clinical trial involving 45 obese patients, recruited from the Obesity Unit of the National Institute of Nutrition between March and August 2022 divided into three groups: diet only (low‐carbohydrate and reduced energy diet), prebiotics (30 g of carob/day) and probiotics (one tablet containing Bifidobacterium longum, Lactobacillus helveticus, Lactococcus lactis, Streptococcus thermophilus/day). The three groups were matched for age, sex and BMI. Patients were seen after 1 month from the intervention. Anthropometric measures, biological parameters, dietary survey and psychological scores were performed. Results The average age of our population was 48.73 ± 7.7 years, with a female predominance. All three groups showed a significant decrease in weight, BMI and waist circumference with p

The aim of the present work was to study the effect of season on phospholipids and triacylglycerols (TAG) of mantle and tentacles of female and male wild Sepia officinalis. The identified phospholipids were phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), phosphatidylserine (PtdSer), and phosphatidylinositol (PtdIns), and PtdEtn was the major fraction. Results showed apparent seasonal variation of phospholipid content, particularly with female samples. Fatty acid composition of phospholipid classes showed a differentiation much more in the proportions than in the diversity of fatty acids. Results showed that the major saturated fatty acids were 16:0 and 18:0, the major monounsaturated fatty acids were 18:1 and 20:l, and the major polyunsaturated fatty acids were docosahexaenoic acid (22:6n‐3) (DHA) and eicosapentaenoic acid (20:5n‐3) (EPA). The results relative to TAG demonstrated significant variations. Principal component analysis confirmed the seasonal and sexual effects. This study could be appropriate for the improvement of consistent monitoring of phospholipid and TAG accumulation in cephalopod, which might be important for both physiological studies and food industries. [ABSTRACT FROM AUTHOR]

A single birth-dose of Hepatitis B vaccine (HepB) can protect newborns from acquiring Hepatitis B infection through vertical transmission, though several follow-up doses are required to induce long-lived protection. In addition to stimulating antibodies, a birth-dose of HepB might also induce polyfunctional CD4+ T-cells, which may contribute to initial protection. We investigated whether vaccination with HepB in the first week of life induced detectable antigen-specific CD4+ T-cells after only a single dose and following completion of the entire HepB vaccine schedule (3 doses). Using HBsAg- stimulated peripheral blood mononuclear cells from 344 infants, we detected increased populations of antigen-specific polyfunctional CD154+IL-2+TNFα+ CD4+ T-cells following a single birth-dose of HepB in a proportion of infants. Frequencies of polyfunctional T-cells increased following the completion of the HepB schedule but increases in the proportion of responders as compared to following only one dose was marginal. Polyfunctional T-cells correlated positively with serum antibody titres following the birth dose (day30) and completion of the 3-dose primary HepB vaccine series (day 128). These data indicate that a single birth dose of HepB provides immune priming for both antigen-specific B- and T cells

Abstract Background SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment. Methods Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 μg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29. Discussion The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection. Trial Registration: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020.

Krukenberg tumors (TK) define themselves as ovarian metastases from cancer more often digestive. These are rare tumors which represent 1 to 2% of ovarian tumors. They are characterized by the presence of “kitten ring” cells filled with mucus and a pseudo-sarcomatous proliferation of the ovarian stroma. Their evolution is quickly fatal. We report 1 case of Krukenberg tumor observed and operated on in June 2020 at the surgery Department B CHU Constantine. The symptoms began with a rectal syndrome with transient episodes of pelvic pain. In this regard, we will recall the epidemiological, clinical and evolutionary characteristics of this disease.

Vegetal diamine oxidase (vDAO), an enzyme proposed to relieve symptoms of histaminosis, shows better reactivity with histamine and aliphatic diamines, as well as higher enzymatic activity than DAO of animal origin. The objective of this study was to evaluate the enzyme activity of vDAO from germinating grains from Lathyrus sativus (grass pea) and Pisum sativum (pea), and to verify the presence of a neurotoxin, β-N-Oxalyl-L-α,β-diaminopropionic acid (β-ODAP), in the crude extract obtained from their seedlings. A targeted liquid chromatography–multiple-reaction monitoring mass spectrometry method was developed and used to quantify β-ODAP in the analysed extracts. An optimized sample preparation procedure, involving protein precipitation with acetonitrile followed by mixed-anion exchange solid-phase extraction, allowed for high sensitivity and good peak shape for β-ODAP detection. The Lathyrus sativus extract exhibited the highest vDAO enzyme activity of the extracts, followed by the extract from pea cultivar Amarillo from the Crop Development Centre (CDC). The results have also shown that even though β-ODAP was present in the crude extract from L. sativus, its content was far below the toxicity threshold (300 mg of β-ODAP/kg body/day). CDC Amarillo showed 5000-fold less β-ODAP than the undialysed L. sativus extract. It was concluded that both species can be considered as convenient sources of vDAO for potential therapeutic use.

In vertebrates, the octopeptide angiotensin II (AngII) is an important in vivo regulator of the cardiovascular system. It acts mainly through two G protein-coupled receptors, AT1 and AT2. To better understand distinctive features of these receptors, we carried out a phylogenetic analysis that revealed a mirror evolution of AT1 and AT2, each one split into two clades, separating fish from terrestrial receptors. It also revealed that hallmark mutations occurred at, or near, the sodium binding site in both AT1 and AT2. Electrostatics computations and molecular dynamics simulations support maintained sodium binding to human AT1 with slow ingress from the extracellular side and an electrostatic component of the binding free energy around -3kT, to be compared to around -2kT for human AT2 and the δ opioid receptor. Comparison of the sodium binding modes in wild type and mutated AT1 and AT2 from humans and eels indicates that the allosteric control by sodium in both AT1 and AT2 evolved during the transition from fish to amniota. The unusual S7.46N mutation in AT1 is mirrored by a L3.36M mutation in AT2. In the presence of sodium, the N7.46 pattern in amniota AT1 stabilizes the inward orientation of N3.35 in the apo receptor, which should contribute to efficient N3.35 driven biased signaling. The M3.36 pattern in amniota AT2 favours the outward orientation of N3.35 and the receptor promiscuity. Both mutations have physiological consequences for the regulation of the renin-angiotensin system. Author summary The analysis of protein sequences from different species can reveal interesting trends in the structural and functional evolution of a protein family. Here, we analyze the evolution of two G protein-coupled receptors, AT1 and AT2, which bind the angiotensin II peptide and are important regulators of the cardiovascular system. We show that these receptors underwent a mirror evolution. Specific mutations at, or near, the sodium binding pocket occurred in both AT1 and AT2 during the transition to terrestrial life. We carried out electrostatics computations and molecular dynamics simulations to decipher the details of the sodium binding mode in eel and human receptors, as prototypes of fish and amniota receptors. Our results indicate that sodium binding is kinetically slow but thermodynamically stable. Comparison of the sodium binding modes in eel and human receptors reveals that an unusual mutation in the sodium binding pocket of AT1 is critical for biased signaling of amniota AT1 whereas a mutation in AT2 promotes promiscuity of amniota AT2. In turn, these data indicate that a few mutations at a strategic position (here the sodium binding pocket) are an efficient way to gain functional evolution.

Abstract The ribotoxin deoxynivalenol (DON) is a trichothecene found on cereals responsible for mycotoxicosis in both humans and farm animals. DON toxicity is characterized by reduced food intake, diminished nutritional efficiency and immunologic effects. The present study was designed to further characterize the alterations in energy metabolism induced by DON intoxication. We demonstrated that acute DON intoxication triggered liver steatosis associated with an altered expression of genes related to lipids oxidation, lipogenesis and lipolysis. This steatosis was concomitant to anorexia, hypoglycemia and a paradoxical transient insulin release. DON treatment resulted also in stimulation of central autonomic network regulating sympathetic outflow and adrenaline and glucocorticoids secretion. Furthermore, an increased expression of genes linked to inflammation and reticulum endoplasmic stress was observed in the liver of DON-treated mice. Finally, we propose that lipids mobilization from adipose tissues (AT) induced by DON intoxication drives hepatic steatosis since (1) genes encoding lipolytic enzymes were up-regulated in AT and (2) plasma concentration of triglycerides (TGs) and non-esterified fatty acids were increased during DON intoxication. Altogether, these data demonstrate that DON induced hormonal and metabolic dysregulations associated with a spectrum of hepatic abnormalities, evocative of a non-alcoholic fatty liver disease.

BackgroundUser experience (UX), including usability, should be formally assessed multiple times throughout the development process to optimize the acceptability and integration of a new technology before implementing it within the home environment of people living with cognitive impairments. ObjectiveThe aim of this study is to identify UX issues, notably usability issues, and factors to consider for the future implementation of the COOK (Cognitive Orthosis for Cooking) within the home of individuals with traumatic brain injury (TBI) to identify modifications to improve the technology. MethodsThis study comprised two rounds of UX evaluations, including extensive usability testing, which were completed in a laboratory context: 3 sessions with 5 experts and, after improvement of COOK, 2 sessions with 10 participants with TBI. Each session included the use of scenarios and questionnaires on UX and usability. ResultsBoth rounds demonstrated good usability outcomes and hedonic qualities. Various usability issues were identified by participants, such as navigation inconsistencies, technical bugs, and the need for more feedback. Factors to consider in the future implementation of COOK were also mentioned by participants with TBI, including environmental (eg, space available and presence of pets) and personal factors (eg, level of comfort with technology, presence of visual deficits, and preferences). ConclusionsBy evaluating UX, including usability, various times throughout the development process and including experts and end users, our research team was able to develop a technology that was perceived as usable, pleasant, and well-designed. This research is an example of how and when people with cognitive impairments (ie, people with TBI) can be involved in evaluating the UX of new technology.

The world’s fragmented response to the COVID-19 pandemic created fertile ground for mixed messages and inconsistency. The authors analyzed Google-trending insights from five countries (Italy, Spain, the United States, the United Kingdom, and France) across three-week time (1–23 March 2020) to document trends in population health anxiety in response to the initial global spreading of the outbreak. The results are expressed in the form of Uncertainty Index (UI), which reflects the total number of Google searches/COVID-19 prevalence and standardized per million inhabitants. The United Kingdom experienced the highest level of health anxiety (UI = 11.5), followed by France (UI = 4.6) and Spain (UI = 3.2). The United States suffered the highest rate of uncertainty in the early stage of the pandemic; the Italian population experienced a balanced level of anxiety. Institutionalizing risk communication during COVID-19 should represent an integral part of the country emergency response.

The aim of this study was to characterize the prevalence of fecal carriage of extended-spectrum beta-lactamases and carbapenemase-producing Gram-negative bacteria among healthy humans in Tunisia. Fifty-one rectal swabs of healthy volunteers were plated on MacConkey agar plates supplemented with cefotaxime or imipenem. The occurrences of resistance genes, integrons, and phylogroup typing were investigated using PCR and sequencing. The genetic relatedness of isolates was determined by pulsed-field-gel-electrophoresis (PFGE) and multilocus-sequence-typing (MLST). Whole-genome-sequencing (WGS) was performed for the carbapenem-resistant isolate. Sixteen ESBL-producing Escherichia coli isolates and one carbapenem-resistant Enterobacter bugandensis were detected out of the fifty-one fecal samples. The ESBL-producing E. coli strains contained genes encoding CTX-M-15 (n = 9), CTX-M-1 (n = 3), CTX-M-27 (n = 3), and CTX-M-55 (n = 1). Three CTX-M-1-producers were of lineages ST131, ST7366, and ST1158; two CTX-M-15-producers belonged to lineage ST925 and ST5100; one CTX-M-27-producer belonged to ST2887, and one CTX-M-15-producer belonged to ST744. Six isolates contained class 1 integrons with the following four gene cassette arrangements: dfrA5 (two isolates), dfrA12-orf-aadA2 (two isolates), dfrA17-aadA5 (one isolate), and aadA1 (one isolate). E. bugandensis belonged to ST1095, produced IMI-2 carbapenemase, and contained qnrE1 and fosA genes. A genome-sequence analysis of the E. bugandensis strain revealed new mutations in the blaACT and qnr genes. Our results reveal an alarming rate of ESBL-E. coli in healthy humans in Tunisia and the first description of IMI-2 in E. bugandensis.

Background: Taste disorders (TDs) have been reported to be very common in patients suffering from coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus. In most of the hitherto conducted studies, a gustatory assessment was performed on the basis of surveys or self-reports by patients. The aim of our study was to undertake an objective assessment of four basic taste qualities by conducting tasting sessions that allowed detection thresholds in COVID-19 Tunisian patients and to study their associations with inflammation. Methods: This analytical cross-sectional study was conducted on 89 patients aged between 21 to 70 years who had been diagnosed with COVID-19. We used Burghart taste strips to assess taste perception of the four taste qualities, i.e., sour, bitter, sweet, and salty. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) were measured. Results: Taste disorders were reported by 40.4% of the patients, while objective assessments revealed that 63.8% of participants were suffering from hypogeusia and/or ageusia. Sour taste was the most altered (70.8%) gustatory quality. Patients with severe COVID-19 had significantly lower sour and bitter taste scores when compared to patients with minor/moderate forms. There was no significant association between serum inflammatory markers and taste disorders. However, the relationship between bitter and sweet taste qualities and IL-1β levels was significant (p = 0.018 and p = 0.041). Conclusions: Our results demonstrate the interest in the objective assessment of taste dysfunctions in COVID-19 patients.

This study sought to analyze the antimicrobial resistant phenotypes and genotypes as well as the virulence content of S. aureus isolates recovered from patients with diabetic foot infections (DFIs) in a Tunisian hospital. Eighty-three clinical samples of 64 patients were analyzed, and bacterial isolates were identified by MALDI-TOF. The antimicrobial resistance phenotypes were determined by the Kirby–Bauer disk diffusion susceptibility test. Resistance and virulence genes, agr profile, spa and SCCmec types were determined by PCR and sequencing. S. aureus was detected in 14 of the 64 patients (21.9%), and 15 S. aureus isolates were recovered. Six out of the fifteen S. aureus isolates were methicillin-resistant (MRSA, mecA-positive) (40%). The isolates harbored the following resistance genes (number of isolates): blaZ (12), erm(B) (2), erm(A) (1), msrA (2), tet(M) (2), tet(K) (3), tet(L) (1), aac(6′)-aph(2″) (2), ant(4″) (1) and fexA (1). The lukS/F-PV and tst genes were detected in three isolates. Twelve different spa-types were identified and assigned to seven clonal complexes with the predominance of agr-type III. Furthermore, the SCCmec types III, IV and V were found among the MRSA isolates. Moreover, one MSSA CC398-t571-agr-III isolate was found; it was susceptible to all antimicrobial agents and lacked luk-S/F-PV, tst, eta and etb genes. This is the first report on the prevalence and molecular characterization of S. aureus from DFIs and also the first detection of the MSSA-CC398-t571 clone in human infections in Tunisia. Our findings indicated a high prevalence S. aureus in DFIs with genetic diversity among the MSSA and MRSA isolates.

In Australia, there is a paucity of data about the extent and impact of zoonotic tick-related illnesses. Even less is understood about a multifaceted illness referred to as Debilitating Symptom Complexes Attributed to Ticks (DSCATT). Here, we describe a research plan for investigating the aetiology, pathophysiology, and clinical outcomes of human tick-associated disease in Australia. Our approach focuses on the transmission of potential pathogens and the immunological responses of the patient after a tick bite. The protocol is strengthened by prospective data collection, the recruitment of two external matched control groups, and sophisticated integrative data analysis which, collectively, will allow the robust demonstration of associations between a tick bite and the development of clinical and pathological abnormalities. Various laboratory analyses are performed including metagenomics to investigate the potential transmission of bacteria, protozoa and/or viruses during tick bite. In addition, multi-omics technology is applied to investigate links between host immune responses and potential infectious and non-infectious disease causations. Psychometric profiling is also used to investigate whether psychological attributes influence symptom development. This research will fill important knowledge gaps about tick-borne diseases. Ultimately, we hope the results will promote improved diagnostic outcomes, and inform the safe management and treatment of patients bitten by ticks in Australia.

Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline – an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their “dispositional endotype” at pre-vaccination baseline, could dictate response to vaccination.

The first week of life impacts health for all of life, but the mechanisms are little-understood. Here the authors extract multi-omic data from small volumes of blood to study the dynamic molecular changes during the first week of life, revealing a robust developmental trajectory common to different populations.

Peritoneal mesotheliomas are very rare tumors. Their prognosis is poor, average survival does not exceed 1 year after peritoneal cytoreduction. Systemic chemotherapy is considered to have no proven value in the management of peritoneal mesotheliomas. Objective responses with systemic chemotherapy are very rare. We report here a case of an advanced peritoneal mesothelioma which achieved an unexpected partial response with chemotherapy, allowing the patient to have a right colectomy. The patient was referred to a specialized center on HIPEC, but taking in account the long awaiting interval, the HIPEC was judged to be inefficient and then the poursuit of 6 cycles of systemic chemotherapy was decided. The patient is still alive without any symptom and with a good performance status at 59 months after diagnosis. Throughout our case, we provide an encouraging evidence of the role of initial systemic chemotherapy in the downstaging of initially unresectable primary malignant mesothelioma and in the improvement of overall survival.

The Expanded Program for Immunization Consortium – Human Immunology Project Consortium study aims to employ systems biology to identify and characterize vaccine-induced biomarkers that predict immunogenicity in newborns. Key to this effort is the establishment of the Data Management Core (DMC) to provide reliable data and bioinformatic infrastructure for centralized curation, storage, and analysis of multiple de-identified “omic” datasets. The DMC established a cloud-based architecture using Amazon Web Services to track, store, and share data according to National Institutes of Health standards. The DMC tracks biological samples during collection, shipping, and processing while capturing sample metadata and associated clinical data. Multi-omic datasets are stored in access-controlled Amazon Simple Storage Service (S3) for data security and file version control. All data undergo quality control processes at the generating site followed by DMC validation for quality assurance. The DMC maintains a controlled computing environment for data analysis and integration. Upon publication, the DMC deposits finalized datasets to public repositories. The DMC architecture provides resources and scientific expertise to accelerate translational discovery. Robust operations allow rapid sharing of results across the project team. Maintenance of data quality standards and public data deposition will further benefit the scientific community.

BackgroundVaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts.MethodsWe applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.ResultsUsing both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response.ConclusionThis study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.

Distant metastases from breast phyllodes tumor (PT) are very rare. They usually occur in lung and bones. We report a case of a 51-year-old woman who was hospitalized in the digestive surgical department for atypical epigastric pain. Her medical history started 2 years ago when she underwent a curative left mastectomy for a malignant PT of the breast. Radical surgery was indicated to her resectable pancreatic tumor diagnosed on computed tomography. Histological exam confirmed that it was pancreatic metastases of her breast PT. Adjuvant chemotherapy was indicated. Three months after the surgery, the patient developed gallbladder and brain metastases. She died 5 weeks later. With this case, we enrich the literature with another example of pancreatic metastasis from PT and we report, for the first time, gallbladder metastasis. The very high aggressiveness of this tumor suggests that markers of tumor malignancy need to be sought after by subsequent studies.